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Titolo:
CHRONIC EXPOSURE TO MPTP AS A PRIMATE MODEL OF PROGRESSIVE PARKINSONISM - A PILOT-STUDY WITH A FREE-RADICAL SCAVENGER
Autore:
BLANCHET PJ; KONITSIOTIS S; HYLAND K; ARNOLD LA; PETTIGREW KD; CHASE TN;
Indirizzi:
NINCDS,EXPT THERAPEUT BRANCH,NIH,BLDG 10,ROOM 5C103,10 CTR DR MSC 1406 BETHESDA MD 20892 NINCDS,EXPT THERAPEUT BRANCH,NIH BETHESDA MD 20892 BAYLOR UNIV,MED CTR,KIMBERLY H COURTWRIGHT & JOSEPH W SUMMERS INST MEDALLAS TX 00000 UNIV TEXAS,SW MED CTR,DEPT NEUROL DALLAS TX 00000 NIMH,DIV EPIDEMIOL & RES SERV,NIH BETHESDA MD 20892
Titolo Testata:
Experimental neurology
fascicolo: 2, volume: 153, anno: 1998,
pagine: 214 - 222
SICI:
0014-4886(1998)153:2<214:CETMAA>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
STRIATAL DOPAMINE DEFICIENCY; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; CEREBROSPINAL-FLUID; SUBSTANTIA-NIGRA; LIQUID-CHROMATOGRAPHY; MONOAMINE METABOLISM; OXIDATIVE STRESS; COMMON MARMOSETS; DISEASE; NEUROTOXICITY;
Keywords:
PARKINSONS DISEASE; MPTP; MONKEYS; NEUROPROTECTION; OXIDATIVE STRESS; ANTIOXIDANT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
68
Recensione:
Indirizzi per estratti:
Citazione:
P.J. Blanchet et al., "CHRONIC EXPOSURE TO MPTP AS A PRIMATE MODEL OF PROGRESSIVE PARKINSONISM - A PILOT-STUDY WITH A FREE-RADICAL SCAVENGER", Experimental neurology, 153(2), 1998, pp. 214-222

Abstract

The development of a validated primate model of progressive parkinsonism is a critical step in the evaluation of drugs that might halt or slow progression of Parkinson's disease, In this pilot study, we gradually exposed 14 cynomolgus monkeys to 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP), at a weekly dose of 0.5 mg/kg s.c. for 10 weeks, to determine their probability of not reaching a predetermined endpoint on a disability scale by Kaplan-Meier analysis. Four other MPTP-exposed animals were coadministered the potent free radical scavenger -methoxyphenyl)-1-piperazinyl]acetylamino-2,2,4,6- tetramethylindan (OPC-14117)as a single oral daily dose of 0.6 g/kg, starting 2 weeks before MPTP initiation. The risk of reaching endpoint by week 10 was 79% and mean time before reaching endpoint was 6 weeks. Global motor activity,recorded in a subset of animals using a portable activity monitor, declined following the first MPTP dose and never recovered. Several cerebrospinal fluid indices of central monoamine metabolism collected by suboccipital puncture at 0, 5, and 10 weeks, including HVA, DOPAC, and tetrahydrobiopterin but not MHPG, were found to be ''trait'' markers for MPTP exposure, whereas CSF DOPAC and tetrahydrobiopterin constituted potential ''state'' markers for reaching endpoint, The antioxidant OPC-14117 did not protect against MPTP-induced parkinsonism. Further attempts to validate this incremental model of neurotoxin-induced parkinsonism as a predictor of patient responses to putative neuroprotectiveagents appear warranted.

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Documento generato il 01/12/20 alle ore 18:27:57